Étude comparée des gels hydroalcooliques importés et ceux produits au Bénin, vendus dans les supermarchés de la ville de Cotonou / NA

Depuis le début de la crise épidémique liée au virus Covid-19, pour de nombreux citoyens, se laver les mains est devenu un rituel nécessaire. Le gel hydroalcoolique constitue une solution alternative qui a été popularisée par les recommandations des autorités sanitaires dans le cas d'indisponibilité du lavage des mains. Que cela soit en pharmacie, en supermarché, ou sur internet, de nombreux sites de commerce proposent ces produits à la vente. Toutefois l'appellation ne garantit pas l'efficacité de chaque produit vendu. C'est ainsi que la présente étude s'est attelée à l'évaluation de la qualité des gels hydroalcooliques (GHA) utilisés pour la désinfection des mains au cours de la crise sanitaire liée au Coronavirus. Au total, 28 échantillons dont 23 importés et 5 locaux ont été collectés dans 16 supermarchés de la ville de Cotonou. Ils ont été soumis au test d'inspection visuelle, aux tests organoleptiques ainsi qu'aux analyses physico-chimiques et microbiologiques. Au terme de l'étude, 17,86% des GHA ont été déclarés non-conformes par rapport aux inspections visuelles, 39,28% par rapport aux tests organoleptiques, 21% par rapport au pH et à la densité et enfin 21% de non-conformité aux tests microbiologiques. Le taux de non-conformité est plus important dans le camp des gels importés ce qui atteste l'effort des producteurs locaux pour le respect des normes promulguées par les autorités sanitaires

Since the start of the epidemic crisis linked to the Covid-19 virus, for many citizens, washing their hands has become a necessary ritual. Hydroalcoholic gel constitutes an alternative solution which has been popularized by the recommendations of the health authorities in the case of hand washing unavailable. Whether in pharmacies, supermarkets, or on the internet, many shopping sites offered these products for sale. However, this name does not guarantee the effectiveness of each product sold. The present study has been set out to assess the quality of hydroalcoholic gels (GHA) used for hand disinfection during the health crisis linked to the Coronavirus. In total, 28 samples, of which 23 were imported and 5 locals, were collected in 16 supermarkets in the city of Cotonou. They were subjected to visual inspection test, organoleptic tests as well as physico-chemical and microbiological analyzes. At the end of the study, 17.86% of GHAs were declared non-compliant with respect to visual inspections, 39.28% with respect to organoleptic tests, 21% with respect to pH and density and finally 21% of noncompliance with microbiological testing. The rate of non-compliance is higher in the imported gel camp, which attests to the efforts of local producers to comply with the standards promulgated by the health authorities

Simultaneous Determination of a Fixed-Dose Combination of Lercanidipine and Valsartan in Human Plasma by LC-MS-MS: Application to a Pharmacokinetic Study.

A simple, sensitive and reproducible liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the first time for simultaneous quantification of lercanidipine and valsartan in human plasma. The analytes were extracted by simple protein precipitation with acetonitrile and separated on a Hanbon Hedera ODS-2 C18 (150 mm× 2.1 mm, 5 µm) column. The mobile phase was composed of a mixture (53:47, v/v) of acetonitrile and 10 mmol/L ammonium acetate containing 0.5% formic acid. The analytes were ionized by positive electrospray ion and detected in the multi-reaction monitoring mode with m/z 612.1 → 280.2 for lercanidipine, m/z 436.0 → 235.1 for valsartan and m/z 285.1 → 193.1 for diazepam, the internal standard. The calibration curves obtained were linear over the concentration range of 0.01504-10.07 ng/mL for lercanidipine and 5.025-6,030 ng/mL for valsartan. The results of the intra- and inter-day precision studies were within the acceptance range. The recoveries of the analytes were in the range of 98-103%. This method was successfully applied to the pharmacokinetic study of a novel fixed-dose combination of lercanidipine and valsartan formulation after an oral administration to healthy Chinese subjects.

In vitro metabolism of bencycloquidium bromide and its inhibitory effects on human P450 isoenzymes: implication of CYP2D6, CYP2C19 and CYP3A4/5.

Bencycloquidium bromide (BCQB) is a novel selective muscarinic M1/M3 receptor antagonist with potent therapeutic effects on rhinitis and chronic obstructive pulmonary disease. The metabolism of BCQB has been investigated in human liver microsomes and human recombinant P450 to elucidate the P450 isozymes responsible for its metabolism in human. Also, the metabolism pathway and the potency of BCQB in inhibiting CYP's various isozymes in humans were investigated. The main biotransformation route of BCQB was NADPH-dependent oxidation. BCQB was metabolized oxidatively to four metabolites that were identified as monohydroxylated derivatives of BCQB at the phenyl and pentyl moieties of the molecule. The results from in vitro inhibition studies indicated that quinidine inhibited 86 % of metabolism of BCQB, while ticlopidine and ketoconazole inhibited 39 and 29 %, respectively. Inhibition studies with selective chemical inhibitors and incubations with human recombinant P450 isoforms demonstrated that the oxidative metabolism of BCQB is mediated by CYP2D6, CYP2C19 and CYP3A4/5, whereas BCQB had no inhibitory effect on any other P450 isoenzyme in humans.

Study of pharmacokinetic interaction of paroxetine and roxithromycin on bencycloquidium bromide in healthy subjects.

PURPOSE: The aim of this study was to investigate the potential drug-drug interaction between Bencycloquidium bromide (BCQB) and paroxetine, and between BCQB and roxithromycin. METHODS: Two studies were conducted on healthy male Chinese volunteers. Study A was an open-label, two-period, one-sequence crossover study (n=21). Each participant received a single nasal spray dose of BCQB 180µg on day 1. After a 7-day wash-out period, subjects received 20mg of paroxetine from day 8 to 17, and were co-administered 20mg of paroxetine and BCQB 180µg on day 18. In study B, participants (n=12) were randomly assigned to two groups. In period I, group A received BCQB 180µg on day 1, followed by the same dose four times daily from day 4 to 10, then, on day 11 a single dose of 150mg roxithromycin with BCQB 180µg were co-administered. In parallel, group B received a single dose of roxithromycin 150mg on day 1, followed by 300mg of roxithromycin from day 4 to 10, then, on day 11 a single dose of BCQB 180µg with roxithromycin 300mg were co-administered. After a wash-out time of 7days the respective treatments of each group (A and B) were swapped in period II. Blood samples were collected for pharmacokinetic analysis. Statistical comparison of pharmacokinetic parameters was performed to identify a possible drug interaction between treatments. Tolerability was evaluated by recording adverse events. RESULTS: Study A: Geometric mean AUC0-36 for BCQB alone and co-administered with paroxetine were 474.3 and 631.3pgh/ml, respectively. The geometric mean ratio (GMR) of AUC0-36 was 1.33 (1.13-1.46), 90% C.Is, and was out the predefined bioequivalence interval (90% C.Is, 0.80-1.25). Geometric mean Cmax were 187.0 and 181.2pg/ml. Study B: The GMR of AUC0-36 was 0.98 (0.90-1.07), 90% C.Is for BCQB, and the GMR of AUC0-72 was 0.98 (0.87-1.11), 90% C.Is for roxithromycin. Both GMRs were within the predefined bioequivalence interval (90% C.Is, 0.80-1.25). Other pharmacokinetic parameters were within the predefined interval. No serious adverse events were reported and no significant clinical changes were observed in laboratory test results, vital signs and ECGs in any of the studies. All treatments were well tolerated. CONCLUSION: The co-administration of BCQB with paroxetine showed a moderate increase in BCQB exposure, but was not clinically relevant. Also, no drug interaction was found between BCQB and roxithromycin.

In vivo and in vitro evidence of the sex-dependent pharmacokinetics and disposition of G004, a potential hypoglycemic agent, in rats.

G004 is a novel sulfonylurea hypoglycemic drug which aimed at reducing macro- and micro-vascular complications as well as controlling glucose excursion in type 2 diabetes mellitus. The pharmacokinetics of G004 in rats was sex- and dose-dependent over the dose range of 1-10 mg kg(-1). The mean AUC values in the female rats were fivefold higher than those in males. Drug blood and tissue levels in female rats were higher than the most counterparts of males. Compared with male rats, G004 was eliminated slowly from female rats in the bile, urine and feces. Consistent with the in vivo observations, marked sex-related difference of the metabolizing activity between the male and female liver microsomes (RLM) was observed. The intrinsic clearance (V max/K m) of G004 was 3.1-fold larger in the RLM from male than female rats. Seventeen oxidative metabolites were identified in rat liver microsomes. The amount of three metabolites of G004 showed relatively sex-related difference in RLM incubations. CYP2C11 was demonstrated mainly contributing to the sex-related differences in the pharmacokinetics and disposition of G004 in rats.

Gradient elution mode for the troubleshooting of matrix effect on the determination of G004 in different tissues by LC-MS/MS.

A steep gradient elution mode was applied to reduce the risk of matrix effect (ME) for the determination of G004, a novel sulfonylurea hypoglycemic drug, in a tissue distribution study by LC-MS/MS. The mass spectra of the total-ion-current chromatograms combined with the post-column infusion traces enabled the 'unseen' interfering species to be directly detected, and ensured that the chromatography conditions and sample preparation method were adequate to overcome the ME. According to this, a steep gradient elution mode was designed to overcome the intense ME from different tissues. The analysis was performed by monitoring the transitions m/z 558.1 → 419.0 for G004 and m/z 489.3 → 364.1 for glimepiride used as the internal standard. Calibration curves recovered over a range from 0.1 to 10000 ng/mL for seven different tissues. Sex-related difference was found in the tissue distribution. The drug levels in the tissues of female rats were about two to three times higher than those in male counterparts. The highest level was observed in liver, then in kidney, heart, pancreas, lung and spleen, but no G004 was detected in brain. G004 was slowly eliminated from female rats compared with male rats. There was no long-term accumulation of G004 in male or female rat tissues.

Simultaneous determination of rabeprazole and its two active metabolites in human urine by liquid chromatography with tandem mass spectrometry and its application in a urinary excretion study.

A simple and rapid liquid chromatography with tandem mass spectrometry method has been developed and validated for the determination of rabeprazole and its two active metabolites, rabeprazole thioether and desmethyl rabeprazole thioether, in human urine using donepezil as the internal standard. The sample preparation procedure involved a simple dilution of urine sample with methanol (1:3, v/v). The chromatographic separation was achieved on a Hedera ODS-2 C18 column using a mixture of methanol/10 mmol/L ammonium acetate solution (containing 0.05% formic acid; 55:45, v/v) as the mobile phase. The method was validated over the concentration ranges of 0.15-100 ng/mL for rabeprazole, 0.30-400 ng/mL for rabeprazole thioether, and 0.05-100 ng/mL for desmethyl rabeprazole thioether. The established method was highly sensitive with a lower limit of quantification of 0.15 ng/mL for rabeprazole, 0.30 ng/mL for rabeprazole thioether, and 0.05 ng/mL for desmethyl rabeprazole thioether. The intra- and interbatch precision was <4.5% for the low, medium, and high quality control samples of all the analytes. The recovery of the analytes was in the range 95.4-99.0%. The method was successfully applied to a urinary excretion profiles after intravenous infusion administration of 20 mg rabeprazole sodium in healthy volunteers.

Pharmacokinetics of levosulpiride after single and multiple intramuscular administrations in healthy Chinese volunteers.

The main purpose of this study was to evaluate the pharmacokinetics of levosulpiride in humans after single and multiple intramuscular injections. Six males and six females received single dose of either 25 mg or 50 mg levosulpiride, or multiple doses of 25 mg every 12 h for 5 consecutive days. In the single 25 mg study, the mean peak plasma concentration (C max) was 441 ng/mL, the mean area under the concentration-time curve from 0 to 36 h (AUC0-36) was 1724 ng h/mL, and the mean elimination half-life (t 1/2) was 7.0 h. In the single 50 mg study, the mean C max was 823 ng/mL, the mean AUC0-36 was 3748 ng·h/mL, and the mean t 1/2 was 6.8 h. After multiple doses of 25 mg levosulpiride, the average plasma concentration (C av) was 136 ng/mL, the fluctuation index (DF) was 3.60, and the accumulation ratio (R) was 1.2. Levosulpiride injections appeared to be well tolerated by the subjects, and can be used for successive administration.